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Serum metabolomics reveals many novel metabolic markers of heart failure, including pseudouridine and 2-oxoglutarate
Dunn, W. B. And Broadhurst; Deepak, S. M.; Buch, M. H. et al.
2007In Metabolomics, 3 (4), p. 413-426
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Keywords :
2-oxoglutarate; Biomarkers; Heart failure; Metabolomics; Pseudouridine
Abstract :
There is intense interest in the identification of novel biomarkers which improve the diagnosis of heart failure. Serum samples from 52 patients with systolic heart failure (EF< 40% plus signs and symptoms of failure) and 57 controls were analyzed by gas chromatography - time of flight - mass spectrometry and the raw data reduced to 272 statistically robust metabolite peaks. 38 peaks showed a significant difference between case and control (p <5 × 10-5). Two such metabolites were pseudouridine, a modified nucleotide present in t- and rRNA and a marker of cell turnover, as well as the tricarboxylic acid cycle intermediate 2-oxoglutarate. Furthermore, 3 further new compounds were also excellent discriminators between patients and controls: 2-hydroxy, 2-methylpropanoic acid, erythritol and 2,4,6-trihydroxypyrimidine. Although renal disease may be associated with heart failure, and metabolites associated with renal disease and other markers were also elevated (e.g. urea, creatinine and uric acid), there was no correlation within the patient group between these metabolites and our heart failure biomarkers, indicating that these were indeed biomarkers of heart failure and not renal disease per se. These findings demonstrate the power of data-driven metabolomics approaches to identify such markers of disease. © Springer Science+Business Media, LLC 2007.
Disciplines :
Cardiovascular & respiratory systems
Author, co-author :
Dunn, W. B. And Broadhurst;  The Manchester Centre for Integrative Systems Biology, Manchester Interdisciplinary Biocentre, The University of Manchester, 131 Princess St., Manchester M1 7DN, United Kingdom
Deepak, S. M.;  School of Chemistry, Manchester Interdisciplinary Biocentre, The University of Manchester, 131 Princess St., Manchester M1 7DN, United Kingdom
Buch, M. H.;  Division of Cardiovascular and Endocrine Sciences, The University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PL, United Kingdom
McDowell, G.;  Department of Cardiology, South Manchester University Hospital, Southmoor Road, Wythenshawe, Manchester M23 9LT, United Kingdom
Spasic, I.;  Department of Clinical Biochemistry, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, United Kingdom
Ellis, D. I.
Brooks, N.
Kell, D. B.
Neyses, Ludwig ;  University of Luxembourg > Rectorate > Research Service
External co-authors :
yes
Title :
Serum metabolomics reveals many novel metabolic markers of heart failure, including pseudouridine and 2-oxoglutarate
Publication date :
2007
Journal title :
Metabolomics
ISSN :
1573-3882
Volume :
3
Issue :
4
Pages :
413-426
Peer reviewed :
Peer reviewed
Commentary :
cited By 74 Scopus
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